Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage

Effect of surgeon and hospital characteristics on outcome after pyloromyotomy

Background: Previous studies have suggested that the outcome after pyloromyotomy is improved with increased surgeon experience. Others have proposed that infants with pyloric stenosis are best treated by specialty-trained pediatric surgeons or at children\u27s hospitals. Hypothesis: Surgeon and hospital characteristics affect complications, length of stay, and hospital charges after pyloromyotomy. Design: Data for a nationally representative sample of infants (n=1277) who underwent pyloromyotomy in 2000 in the United States were obtained from the Kids\u27 Inpatient Database. Surgeon and hospital volumes were stratified into quintiles. Multivariate analyses were performed to analyze the impact of surgeon and hospital volume on length of stay, charges, and major operative complications using models that accounted for the hierarchical structure of patient-, surgeon-, and hospital-level covariates. Results: No association between surgeon volume and either length of stay or charges was observed. Higher surgeon volume, however, was associated with fewer complications (P\u3c.001). Surgeons with the highest volume had a 90% lower risk of complications than those with the lowest volume. Higher hospital volume was associated with shorter length of stay (P\u3c.001). No association between hospital volume and either charges or risk of complications was observed. Conclusions: Higher surgeon and hospital volumes are associated with better outcome among infants who are treated for pyloric stenosis. Identification of aspects of medical and surgical treatment that account for this finding may lead to improvement in the outcome of infants undergoing pyloromyotomy. ©2005 American Medical Association. All rights reserved

Effect of surgeon and hospital characteristics on outcome after pyloromyotomy

Background: Previous studies have suggested that the outcome after pyloromyotomy is improved with increased surgeon experience. Others have proposed that infants with pyloric stenosis are best treated by specialty-trained pediatric surgeons or at children\u27s hospitals. Hypothesis: Surgeon and hospital characteristics affect complications, length of stay, and hospital charges after pyloromyotomy. Design: Data for a nationally representative sample of infants (n=1277) who underwent pyloromyotomy in 2000 in the United States were obtained from the Kids\u27 Inpatient Database. Surgeon and hospital volumes were stratified into quintiles. Multivariate analyses were performed to analyze the impact of surgeon and hospital volume on length of stay, charges, and major operative complications using models that accounted for the hierarchical structure of patient-, surgeon-, and hospital-level covariates. Results: No association between surgeon volume and either length of stay or charges was observed. Higher surgeon volume, however, was associated with fewer complications (P\u3c.001). Surgeons with the highest volume had a 90% lower risk of complications than those with the lowest volume. Higher hospital volume was associated with shorter length of stay (P\u3c.001). No association between hospital volume and either charges or risk of complications was observed. Conclusions: Higher surgeon and hospital volumes are associated with better outcome among infants who are treated for pyloric stenosis. Identification of aspects of medical and surgical treatment that account for this finding may lead to improvement in the outcome of infants undergoing pyloromyotomy. ©2005 American Medical Association. All rights reserved

Verhoogd risico op diabetes mellitus type 2 en hart-en vaatziekten na diabetes gravidarum

Objective To determine the longterm risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) for women with a history of gestational diabetes mellitus. Design Systematic review and metaanalysis. Method Two search strategies were used in PubMed and Embase to determine the longterm risks of developing T2D and CVD after a pregnancy complicated by gestational diabetes mellitus. After critical appraisal of the papers found, 11 papers were included, involving a total of 328,423 patients. Absolute and relative risks (RRs) were calculated. Results Eight studies (n=276,829) reported on the longterm risk of T2D and 4 (n=141,048) on the longterm risk of CVD. Followup ranged from 3.5 to 11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of between 0.28% and 15.5%. Women with gestational diabetes were at increased risk of T2D (weighted RR: 13.2 95% CI: 8.520.7) and CVD (weighted RR: 2.0 95% CI: 1.13.7) compared to women without gestational diabetes. Conclusion Women with prior gestational diabetes mellitus have a significantly increased risk of developing T2D and CVD. It is very important that gestational diabetes is recognised as a cardiovascular risk factor in daily practice. It would be desirable to screen this group of women for the presence of hyperglycaemia and other cardiovascular risk factors. Further research is required to be able to specify the longterm risk of T2D and CVD and to demonstrate whether such screening is costeffective. Conflict of interest: none declared. Financial support: none declared

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage